PKM2 Deficiency in Brown Adipocytes Enhances Differentiation and the Expression of Mitochondrial Genes

Abstract

<b>Abstract ID 15100</b> <b>Poster Board 429</b> <b>Abstract</b> The continuous rise of obesity has been associated with various comorbidities including type 2 diabetes (T2DM), cardiovascular disease (CVD), and even some types of cancer thus defining it a global health concern. Notably, brown adipose tissue (BAT) development and regulation has been more recently recognized as a potential approach to assist with patient weight loss, metabolic improvement, and obesity prevention. In previous investigations, pyruvate kinase M2 (PKM2) was identified as a novel modulator of brown adipogenesis. However, its specific molecular mechanisms and its role in brown adipogenesis remain implicit. To better understand the role of PKM2 in brown fat cell differentiation, mouse brown precursor cells were isolated and shRNA-mediated knockdown approach was employed to specifically alter PKM2 expression in brown pre-adipocytes. The effects of PKM2 deficiency on brown adipocyte differentiation and lipid accumulation were then investigated. In addition, we investigated changes in the expression of several hallmark genes of brown adipocytes. Our study demonstrates that PKM2 deficiency enhances brown fat cell differentiation and maintenance as evidenced by the markedly increased expression of differentiation and functional markers including FASN, PCB, perilipin, and UCP1. These results highlight PKM2 as a potential modulator of brown adipogenesis and suggestively, a therapeutic target for the treatment and prevention of obesity through increasing brown fat mass which may lead to enhanced energy expenditure and the subsequent prevention of excess body fat.